Cytokine-Modulating Strategies and Newer Cytokine Targets for Arthritis Therapy

International Journal of Molecular Sciences

Shivaprasad H. Venkatesha²  Steven Dudics¹  Bodhraj Acharya¹  Kamal D. Moudgil¹ 

[1]Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF-1, Suite 380, Baltimore, MD 21201, USA

关键词: autoimmunity;    arthritis;    biologics;    cytokines;    gene therapy;    inflammation;    interleukins;    rheumatoid arthritis;    siRNA;   

DOI  :  10.3390/ijms16010887

来源: mdpi

【 摘 要 】

Cytokines are the key mediators of inflammation in the course of autoimmune arthritis and other immune-mediated diseases. Uncontrolled production of the pro-inflammatory cytokines such as interferon-γ (IFN-γ), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and IL-17 can promote autoimmune pathology, whereas anti-inflammatory cytokines including IL-4, IL-10, and IL-27 can help control inflammation and tissue damage. The pro-inflammatory cytokines are the prime targets of the strategies to control rheumatoid arthritis (RA). For example, the neutralization of TNFα, either by engineered anti-cytokine antibodies or by soluble cytokine receptors as decoys, has proven successful in the treatment of RA. The activity of pro-inflammatory cytokines can also be downregulated either by using specific siRNA to inhibit the expression of a particular cytokine or by using small molecule inhibitors of cytokine signaling. Furthermore, the use of anti-inflammatory cytokines or cytokine antagonists delivered via gene therapy has proven to be an effective approach to regulate autoimmunity. Unexpectedly, under certain conditions, TNFα, IFN-γ, and few other cytokines can display anti-inflammatory activities. Increasing awareness of this phenomenon might help develop appropriate regimens to harness or avoid this effect. Furthermore, the relatively newer cytokines such as IL-32, IL-34 and IL-35 are being investigated for their potential role in the pathogenesis and treatment of arthritis.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.